The proposed research involves defining the detailed mechanisms by which thyroid and glucocorticoid hormones interrelate to control biologic processes in mammalian cells. A cell culture system has been developed which is responsive to physiological concentrations of thyroid hormones. The cells are GH1 cells, a rat growth hormone and prolactin producing pituitary tumor. Physiological concentrations of thyroid hormones increase cell replication rates and independent of cell growth stimulate a 4-6 fold increase in the rate of growth hormone synthesis. Glucocorticoid hormones only minimal control growth hormone synthesis in the absence of thyroid hormone response. Under these conditions growth hormone represents 2-30% of total cell protein synthesis. These responses appear to be mediated by the thyroid hormone nuclear receptor and the glucocorticoid receptor. The mechanism by which thyroid and glucocorticoid hormone control the same biologic response occurs independently of one hormone modulating the cellular concentration or distribution of the other. The mechanism by which both hormones interact to control the same biologic response will be evaluated by determining how both hormone modulate growth hormone mRNA levels in the cells. In addition, we will characterize the glucocorticoid receptor in GH1 cells and also examine the influence of one hormone on controlling the distribution of the receptor for the other in the fraction of chromatin active in transcription. In addition, we intend to isolate and purify the growth hormone mRNA and develop a cDNA probe to further clarify the detailed mechanism of the induction process by the hormones. It is hoped that these studies will help further clarify the mechanism of thyroid and glucocorticoid hormone action and provide information of multihormonal interrelationships in the regulation of normal and neoplastic mammalian cells.